The project aims at further clarify the mechanism(s) of benzene toxicity and the role of low level occupational benzene exposures by integrating individual exposure data, biological markers of dose, and susceptibility with early and delayed health outcomes in the same study populations.
Information about causal mechanisms will be gathered through the conduction of a cross-sectional biomarkers study on exposure-stratified samples of active workers. Cohorts of European workers exposed to low levels of benzene (range 0.01-10 ppm) have been identified (No.=80,000), including petrochemical workers from Bulgaria, Italy and Great Britain, filling station attendants and traffic wardens from Genoa and Milan in Italy, and bus drivers from Genoa.
A cross-sectional study will be conducted on samples of actively employed workers from each of the selected cohorts, with controls chosen from suitable non-exposed populations. Biomarkers will be employed to precisely characterise individual exposure levels. The markers to be used include trans,trans-muconic acid in urine as a marker of internal dose; benzene oxide-hemoglobin-S-phenylcysteine adduct as a marker of biologically effective dose; and differential white blood cell count, and single strand breaks in leukocyte DNA as markers of early biological effect. The study will determine the genotype of each individual, with respect to polymorphisms of the CYP2E1 and NQO1 genes, to address the hypothesis that individual differences in sensitivity to the biological effects of benzene exposure may be related to genetic differences in the function of these benzene metabolising genes.
Information about the cancer risk associated with low levels of exposure to benzene will be generated by the conduct of an historical mortality study among the European cohorts and results compared with those from other studies. The focus of this work will be on the Italian and Bulgarian cohorts, for which either little (Italian) or no (Bulgarian) previous data have been generated. This part of the project will include workers actively employed between 1970 and 1980, with a follow-up period of 30 years. Standardised Mortality Ratio analysis will be done to adjust for intercountry specific differences in background mortality.
Benzene, Cancer, Occupation, Biomarkers, Epidemiology, Genetic Susceptibility.
Funding SchemeCSC - Cost-sharing contracts
LE1 9HN Leicester
LE1 7DD Leicester